19 research outputs found

    Expression of Ο-protocadherin is negatively regulated by the activation of the β-catenin signaling pathway in normal and cancer colorectal enterocytes.

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    Mu-protocadherin (MUCDHL) is an adhesion molecule predominantly expressed by colorectal epithelial cells which is markedly downregulated upon malignant transformation. Notably, treatment of colorectal cancer (CRC) cells with mesalazine lead to increased expression of MUCDHL, and is associated with sequestration of β-catenin on the plasma membrane and inhibition of its transcriptional activity. To better characterize the causal relationship between β-catenin and MUCDHL expression, we performed various experiments in which CRC cell lines and normal colonic organoids were subjected to culture conditions inhibiting (FH535 treatment, transcription factor 7-like 2 siRNA inactivation, Wnt withdrawal) or stimulating (LiCl treatment) β-catenin activity. We show here that expression of MUCDHL is negatively regulated by functional activation of the β-catenin signaling pathway. This finding was observed in cell culture systems representing conditions of physiological stimulation and upon constitutive activation of β-catenin in CRC. The ability of MUCDHL to sequester and inhibit β-catenin appears to provide a positive feedback enforcing the effect of β-catenin inhibitors rather than serving as the primary mechanism responsible for β-catenin inhibition. Moreover, MUCDHL might have a role as biomarker in the development of CRC chemoprevention drugs endowed with β-catenin inhibitory activity

    Plastic breeze: Volatile organic compounds (VOCs) emitted by degrading macro- and microplastics analyzed by selected ion flow-tube mass spectrometry

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    Pollution from microplastics (MPs) has become one of the most relevant topics in environmental chemistry. The risks related to MPs include their capability to adsorb toxic and harmful molecular species, and to release additives and degradation products into ecosystems. Their role as a primary source of a broad range of harmful volatile organic compounds (VOCs) has also been recently reported.In this work, we applied a non-destructive approach based on selected-ion flow tube mass spectrometry (SIFT-MS) for the characterization of VOCs released from a set of plastic debris collected from a sandy beach in northern Tuscany.The interpretation of the individual SIFT-MS spectra, aided by principal component data analysis, allowed us to relate the aged polymeric materials that make up the plastic debris (polyethylene, polypropylene, and polyethylene terephthalate) to their VOC emission profile, degradation level, and sampling site. The study proves the potential of SIFT-MS application in the field, as a major advance to obtain fast and reliable information on the VOCs emitted from microplastics. The possibility to obtain qualitative and quantitative data on plastic debris in less than 2 min also makes SIFT-MS a useful and innovative tool for future monitoring campaigns involving statistically significant sets of environmental samples

    New methodologies for the detection, identification, and quantification of microplastics and their environmental degradation by-products

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    Sampling, separation, detection, and characterization of microplastics (MPs) dispersed in natural water bodies and ecosystems is a challenging and critical issue for a better understanding of the hazards for the environment posed by such nearly ubiquitous and still largely unknown form of pollution. There is still the need for exhaustive, reliable, accurate, reasonably fast and cost efficient analytical protocols allowing the quantification not only of MPs, but also of nanoplastics (NPs) and of the harmful molecular pollutants that may result from degrading plastics. Here a set of newly developed analytical protocols, integrated with specialized techniques such as pyrolysis-gaschromatography-mass spectrometry (Py-GC/MS), for the accurate and selective determination of the polymers most commonly found as MPs polluting marine and freshwater sediments are presented. In addition, the results of an investigation on the low molecular weight volatile organic compounds (VOCs) released upon photo-oxidative degradation of microplastics highlight the important role of photoinduced fragmentation at a molecular level both as a potential source of hazardous chemicals and as accelerators of the overall degradation of floating or stranded plastic debris

    Expression of Ο-protocadherin is negatively regulated by the activation of the β-catenin signaling pathway in normal and cancer colorectal enterocytes

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    Mu-protocadherin (MUCDHL) is an adhesion molecule predominantly expressed by colorectal epithelial cells which is markedly downregulated upon malignant transformation. Notably, treatment of colorectal cancer (CRC) cells with mesalazine lead to increased expression of MUCDHL, and is associated with sequestration of β-catenin on the plasma membrane and inhibition of its transcriptional activity. To better characterize the causal relationship between β-catenin and MUCDHL expression, we performed various experiments in which CRC cell lines and normal colonic organoids were subjected to culture conditions inhibiting (FH535 treatment, transcription factor 7-like 2 siRNA inactivation, Wnt withdrawal) or stimulating (LiCl treatment) β-catenin activity. We show here that expression of MUCDHL is negatively regulated by functional activation of the β-catenin signaling pathway. This finding was observed in cell culture systems representing conditions of physiological stimulation and upon constitutive activation of β-catenin in CRC. The ability of MUCDHL to sequester and inhibit β-catenin appears to provide a positive feedback enforcing the effect of β-catenin inhibitors rather than serving as the primary mechanism responsible for β-catenin inhibition. Moreover, MUCDHL might have a role as biomarker in the development of CRC chemoprevention drugs endowed with β-catenin inhibitory activity

    Risk factors for pulmonary air leak and clinical prognosis in patients with COVID-19 related acute respiratory failure: a retrospective matched control study.

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    Background- The role of excessive inspiratory effort in promoting alveolar and pleural rupture resulting in air leak (AL) in patients with SARS-CoV-2 induced acute respiratory failure (ARF) while on spontaneous breathing is undetermined. Methods- Among all patients with COVID-19 related ARF admitted to a respiratory intensive care unit (RICU) and receiving non-invasive respiratory support, those developing an AL were and matched 1:1 (by means of PaO2/FiO2 ratio, age, body mass index-BMI and subsequent organ failure assessment [SOFA]) with a comparable population who did not (NAL group). Esophageal pressure (ΔPes) and dynamic transpulmonary pressure (ΔPL) swings were compared between groups. Risk factors affecting AL onset were evaluated. The composite outcome of ventilator-free-days (VFD) at day 28 (including ETI, mortality, tracheostomy) was compared between groups. Results- AL and NAL groups (n=28) showed similar ΔPes, whereas AL had higher ΔPL (20 [16‐21] and 17 [11‐20], p=0.01 respectively). Higher ΔPL (OR=1.5 95%CI[1‐1.8], p=0.01), positive end‐expiratory pressure (OR=2.4 95%CI[1.2‐5.9], p=0.04) and pressure support (OR=1.8 95%CI[1.1-3.5], p=0.03), D-dimer on admission (OR=2.1 95%CI[1.3-9.8], p=0.03), and features suggestive of consolidation on computed tomography scan (OR=3.8 95%CI[1.1-15], p= 0.04) were all significantly associated with AL. A lower VFD score resulted in a higher risk (HR=3.7 95%CI [1.2-11.3], p=0.01) in the AL group compared with NAL. RICU stay and 90-day mortality were also higher in the AL group compared with NAL. Conclusions- In spontaneously breathing patients with COVID‐19 related ARF, higher levels of ΔPL, blood D‐dimer, NIV delivery pressures and a consolidative lung pattern were associated with AL onset

    Studio della correlazione tra le caratteristiche strutturali e i composti organici volatili emessi da polimeri di sintesi a seguito di processi di invecchiamento foto- e termoossidativo

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    Nel corso del presente lavoro di tesi sono stati analizzati campioni di polveri di polimeri di sintesi criomacinati e foto-ossidati artificialmente in camera di invecchiamento tramite lampada allo Xe sia microplastiche invecchiate naturalmente prelevate lungo la costa a Marina di Vecchiano (PI). Entrambi i campioni sono stati analizzati via ATR per calcolarne l’indice carbonilico come parametro attestante l’avvenuta foto-ossidazione del materiale. Inoltre, i campioni invecchiati artificialmente sono stati analizzati via TGA e DSC per comprovarne l’effettivo invecchiamento e, solo i campioni di PS, via GPC per il calcolo dell’indice di polidispersione. I trend dell’indice carbonilico e, per il PS, dell’indice di polidispersione sono stati confrontati con i dati derivanti dall’analisi via NTD-GC/MS dello spazio di testa dei campioni. La procedura di analisi è stata messa a punto valutando il tempo di evoluzione dei VOC emessi dai materiali polimerici e tre sistemi di introduzione dello standard interno. È stato misurato che polveri di polimeri degradate artificialmente presentano emissioni di VOC espresse come μg equivalenti di toluene per grammo di materiale nell’ordine (minimo/massimo) di 10/40 μg per il PET, 1500/3000 μg per l’LDPE, 800/1300 μg per l’HPDE, 700/1700 μg per il PS e 1500/2500 μg per il PP. Inoltre, è stato misurato che l’emissione di VOC di polimeri di sintesi foto-ossidati in condizioni naturali è nell’ordine di 70/200 μg per grammo di materiale

    Selective determination of poly(styrene) and polyolefin microplastics in sandy beach sediments by gel permeation chromatography coupled with fluorescence detection

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    Microplastics generated by plastics waste degradation are ubiquitous in marine and freshwater basins, posing serious environmental concerns. Raman and FTIR spectroscopies, along with techniques such as pyrolysis-GC/MS, are typically used for their identification. We present a procedure based on gel permeation chromatography (GPC) coupled with fluorescence detection for semi-quantitative selective determination of the most common microplastics found in marine shoreline sediments: poly(styrene) (PS) and partially degraded polyolefins (LDPEox). By operating the detector at either 260/280 or 370/420 nm excitation/emission wavelengths PS can be distinguished from LDPEox upon GPC separation. Semi-quantitative determination of microplastics contents is also possible: dichloromethane extracts of PS and LDPEox yield linear plots of fluorescence peak area vs concentration (0-5.0 mg/mL range) and were used as reference materials for quantification of the plastics content in sand samples collected in the winter berm and dune sectors of a Tuscany beach in Italy
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